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The tyrosine kinase MET (hepatocyte growth factor receptor) is activated or mutated in a wide range of cancers and is often correlated with a poor prognosis. Precision medicine with positron emission tomography (PET) can potentially aid in the assessment of tumor biochemistry and heterogeneity, which can prompt the selection of the most effective therapeutic regimes. The selective MET inhibitor PF04217903 (1) formed the basis for a bioisosteric replacement, leading to the deoxyfluorinated analog [18F]2. [18F]2 could be synthesized with a "hydrous fluoroethylation" protocol in 6.3 ± 2.6% radiochemical yield and a molar activity of >50 GBq/μmol. In vitro autoradiography indicated that [18F]2 selectively binds to MET in PC3 tumor tissue, and in vivo biodistribution in mice showed predominantly a hepatobiliary excretion along with a low retention of radiotracer in other organs. [ABSTRACT FROM AUTHOR]

Large-diameter trees are important for both ecological and economic reasons, but they have become increasingly rare. Thus, there is an interest in easily locating such trees, and for this purpose, the use of airborne laser scanning (ALS) seems suitable. Our objective was to assess the accuracy of area-based ALS estimation in predicting the number of large- diameter Scots pines (Pinus sylvestris L.). A sample of 856 trees with a diameter > 35 cm were measured from 1109 sample plots located in eastern Norway. We fitted negative binomial and zero-inflated negative binomial models for predicting large-diameter tree counts. ALS-derived and external variables were used as predictors when fitting the models. The accuracy was assessed based on the weighted kappa coefficient and cross validation. Our best model was based on three ALS height distribution variables, one horizontal ALS variable, and plot elevation. Its overall accuracy was 65.8% and the weighted kappa was 0.55. Although there was a clear relationship between the response and the proposed predictor variables, fairly large errors in the predicted large-diameter tree counts were common. Key words: large trees, LiDAR, area-based method, negative binomial regression, old growth. Les arbres de grand diametre sont importants, a la fois pour des raisons ecologiques et economiques, mais ils sont devenus de plus en plus rares. Il y a donc un interet a localiser facilement ces arbres et l'utilisation du balayage laser aeroporte (BLA) semble appropriee pour ce faire. Notre objectif etait d'evaluer la precision d'une estimation basee sur la surface obtenue par BLA pour predire le nombre de pins sylvestres (Pinus sylvestris L.) de grand diametre. Un echantillon de 856 arbres, d'un diametre > 35 cm, a ete mesure a partir de 1109 placettes echantillons situees dans l'est de la Norvege. Nous avons ajuste des modeles binomiaux negatifs et des modeles binomiaux negatifs a exces de zeros pour predire le nombre d'arbres de grand diametre. Des variables obtenues par BLA et des variables externes ont ete utilisees comme predicteurs lors de l'ajustement des modeles. La precision a ete evaluee sur la base du coefficient kappa pondere et par validation croisee. Notre meilleur modele etait base sur trois variables de distribution de hauteur obtenues par BLA, une variable horizontale obtenue par BLA et l'altitude de la placette. Sa precision globale etait de 65,8 % et le coefficient kappa pondere etait de 0,55. Bien qu'il y ait une relation claire entre la variable de reponse et les variables predictives proposees, d'assez grandes erreurs dans la prediction du nombre d'arbres de grand diametre etaient courantes. [Traduit par la Redaction] Mots-cles: grands arbres, LiDAR, methode d'estimation basee sur la surface, regression binomiale negative, foret ancienne., 1. Introduction Large trees are rare in many forests and difficult to find. They are important for both economic and ecological reasons. Large trees dominate the structure, dynamics, and function [...]

Cabozantinib is an FDA‐approved kinase inhibitor for the treatment of medullary thyroid cancer and advanced renal cell carcinoma, which exerts its therapeutic effect by inhibiting, among others, the tyrosine kinase c‐Met. Noninvasive imaging techniques are becoming increasingly important clinically to ensure drug efficacy, staging, monitoring, and patient stratification. PET isotope labelled tyrosine kinase inhibitors have, for the same reason, potential as PET tracers for imaging of various cancers. On the basis of cabozantinib, we synthesized the novel boronic acid pinacol ester 4 as a labelling precursor, where the boronic ester moiety replaces the fluorine native to this kinase inhibitor. By this, we wanted to explore whether recently developed Cu‐mediated fluorination methods are adaptable to more complex substrates and thereby provide easy access to [18F]cabozantinib directly. Hydrolysis was implemented before preparative purification due to challenges with on‐column hydrolysis of the precursor 4, and [18F]cabozantinib was obtained in ≥99% radiochemical purity and in 2.8 ± 0.05% (n = 4) isolated decay corrected yield in a synthesis time of 90 minutes. The molar activity of representative batches was determined to be 17 ± 8 GBq/μmol. [ABSTRACT FROM AUTHOR]

The protein tubulin is central for maintaining normal cellular processes, and molecules interfering with the tubulin dynamics have potential in the treatment of cancerous diseases. The title compound, C17H14N2O5, was prepared as a lead compound in a project dedicated to the development of therapeutic agents binding to the colchicine binding site on tubulin, thereby interfering with the cell division in cancer cells. It holds many of the main structural characteristics for colchicine binding and has the potential for further modification and functionalization. In the title molecule, the benzene ring is inclined to the quinoline ring by 76.10 (8)°. In the crystal, molecules are linked by two pairs of C--H⋯O hydrogen bonds, forming tubular-like arrangements, propagating along the direction of the diagonals of the ab plane, and enclosing R²2(26) and R²2(16) ring motifs. [ABSTRACT FROM AUTHOR]

Cabozantinib is an FDA-approved kinase inhibitor for the treatment of medullary thyroid cancer and advanced renal cell carcinoma, which exerts its therapeutic effect by inhibiting, among others, the tyrosine kinase c-Met. Noninvasive imaging techniques are becoming increasingly important clinically to ensure drug efficacy, staging, monitoring, and patient stratification. PET isotope labelled tyrosine kinase inhibitors have, for the same reason, potential as PET tracers for imaging of various cancers. On the basis of cabozantinib, we synthesized the novel boronic acid pinacol ester 4 as a labelling precursor, where the boronic ester moiety replaces the fluorine native to this kinase inhibitor. By this, we wanted to explore whether recently developed Cu-mediated fluorination methods are adaptable to more complex substrates and thereby provide easy access to [ 18 F]cabozantinib directly. Hydrolysis was implemented before preparative purification due to challenges with on-column hydrolysis of the precursor 4, and [ 18 F]cabozantinib was obtained in ≥99% radiochemical purity and in 2.8 ± 0.05% (n = 4) isolated decay corrected yield in a synthesis time of 90 minutes. The molar activity of representative batches was determined to be 17 ± 8 GBq/μmol., (Copyright © 2017 John Wiley & Sons, Ltd.)